Inflammation and Activated Innate Immunity in the Pathogenesis of Type 2 Diabetes

Abstract

There is increasing evidence that an ongoing cytokine-induced acute-phase response (sometimes called low-grade inflammation, but part of a widespread activation of the innate immune system) is closely involved in the pathogenesis of type 2 diabetes and associated complications such as dyslipidemia and atherosclerosis. Elevated circulating inflammatory markers such as C-reactive protein and interleukin-6 predict the development of type 2 diabetes, and several drugs with anti-inflammatory properties lower both acute-phase reactants and glycemia (aspirin and thiazolidinediones) and possibly decrease the risk of developing type 2 diabetes (statins). Among the risk factors for type 2 diabetes, which are also known to be associated with activated innate immunity, are age, inactivity, certain dietary components, smoking, psychological stress, and low birth weight. Activated immunity may be the common antecedent of both type 2 diabetes and atherosclerosis, which probably develop in parallel. Other features of type 2 diabetes, such as fatigue, sleep disturbance, and depression, are likely to be at least partly due to hypercytokinemia and activated innate immunity. Further research is needed to confirm and clarify the role of innate immunity in type 2 diabetes, particularly the extent to which inflammation in type 2 diabetes is a primary abnormality or partly secondary to hyperglycemia, obesity, atherosclerosis, or other common features of the disease.

Prevalence of pre-diabetes and type 2 diabetes mellitus among Sami and non-Sami men and women in Northern Norway – The SAMINOR 2 Clinical Survey

“…According to Table 1, both BMI and WHtR in women, and WHtR in men, were higher among Sami individuals. It is believed that adipose tissue in obese people releases higher amounts of non-esterified fatty acids, glycerol, hormones, pro-inflammatory cytokines and other factors which play an important role in the development of dysglycaemia and eventually T2DM [31]. Higher prevalence of obesity (especially abdominal) and its implication in the higher prevalence of T2DM among indigenous peoples have been reported in a number of publications [32–34].…”

Associations of adiponectin with metabolic and vascular risk parameters in the British Regional Heart Study reveal stronger links to insulin resistance-related than to coronory heart disease risk-related parameters

“…Low circulating adiponectin concentrations have been linked to endothelial dysfunction, [5][6][7][8] factors implicated in the pathogenesis of atherosclerosis and diabetes. 9,10 An increasing body of evidence has shown low-adiponectin levels to predict risk of developing diabetes. [11][12][13][14][15][16] Although an inverse association has been found between adiponectin and prevalent coronary heart disease (CHD) in crosssectional studies, 17,18 prospective studies have produced conflicting results.…”

Blood–Brain Barrier Disruption, Vascular Impairment, and Ischemia/Reperfusion Damage in Diabetic Stroke

“…However, in the acute phase, when there is uncontrolled inflammation, the activated microglia, astrocytes, and macrophages can exacerbate damage and/or death to the injured brain by releasing pro‐inflammatory factors and by creating an inhospitable environment for neural repair 123. Both the innate and adaptive immune systems are activated upon inflammation; and DM, stroke, and DM‐stroke can regulate immune response 124. DM induces chronic inflammatory responses including increasing inflammatory mediators that can activate neutrophils and vascular endothelium 91.…”